DNA–RNA hybrids: the risks of DNA breakage during transcription

In this Perspective, the authors consider how DNA breaks stimulate R-loop formation, particularly within actively transcribed genomic regions, and discuss the cellular mechanisms that prevent or remove RNA–DNA hybrids to preserve genome integrity. Although R loops can occur at different genomic locations, the factors that determine their formation and frequency remain unclear. Emerging evidence indicates that DNA breaks stimulate DNA–RNA hybrid formation. Here, we discuss the possibility that formation of hybrids may be an inevitable risk of DNA breaks that occur within actively transcribed regions. While such hybrids must be removed to permit repair, their potential role as repair intermediates remains to be established.